Isolated preparations of Alpha-1-antitrypsin (Alpha1AT), trace-labeled with radioiodine, have been used to obtain data on the turnover of Alpha1AT in normal subjects and patients with Alpha1AT deficiency who have either pulmonary emphysema or chronic hepatocellular disease. The protease inhibitor (Pi) phenotypes of subjects donating plasma for isolation of Alpha1AT and subjects undergoing Alpha1AT turnover studies have been determined. The fractional catabolic rates of M Alpha1AT from normal subjects (phenotype PiMM) and Z Alpha1AT from patients with Alpha1AT deficiency (phenotype PiZZ) are similar in both normal subjects and patients with Alpha1AT deficiency. These findings imply that the low serum Alpha1AT concentration in Alpha1AT deficiency is due to impaired hepatic release of Alpha1AT and that the differences in molecular structure between the Z and M proteins have little effect on the catabolism of Alpha1AT. In common with other glycoproteins, desialylated (i.e. neuraminidase-treated) Alpha1AT is rapidly cleared from plasma by the liver. Pi phenotypes have been determined in populations of patients with rheumatoid arthritis, systemic lupus erythematosis, Sjogren's syndrome and hepatocellular carcinoma.